MX2012012459A

MX2012012459A - Orally disintegrating tablet containing acarbose.

Info

Publication number: MX2012012459A
Application number: MX2012012459A
Authority: MX
Inventors: Tobias Laich; Axel Schneeweis
Original assignee: Bayer Ip Gmbh
Priority date: 2010-04-27
Filing date: 2011-04-26
Publication date: 2012-11-21
Also published as: ES2623025T3; CL2012003011A1; CR20120548A; KR20130062926A; IL222368A0; AU2011247642A1; JP2013525404A; GT201200290A; TWI556823B; KR101788350B1; TW201141490A; UA111155C2; BR112012027303A2; CN102905687A; SG184851A1; CU20120152A7; ECSP12012279A; DOP2012000277A; SI2563329T1; PE20130403A1

Abstract

It was an object of the present invention to provide an orally disintegrating tablet (ODT) for the glycosidase inhibitor acarbose. The object is achieved with an orally disintegrating tablet containing 1â¿¿30% acarbose and 40â¿¿90% water-soluble carrier. In order to obtain the desired properties, the ingredients have to be precompacted and to be premixed with an insoluble carrier.

Description

COMPRESSED BY DESIGNATION BY ORAL ROUTE CONTAINS ACARBOSE FIELD OF THE INVENTION It was an object of the present invention to provide an orally disintegrating tablet (ODT) for the glucosidase acarbose inhibitor. The objective is achieved with an oral disintegration tablet containing 1-30% acarbose and 40-90% water soluble vehicle. In order to obtain the desired properties, it is necessary to pre-compact the ingredients with a soluble lubricant and to pre-mix with a water-soluble vehicle.

BACKGROUND OF THE INVENTION The optimal action of the glucosidase inhibitors as anti-diabetic is achieved by means of a distribution as uniform as possible of the active ingredient in the ingested food. The tablet and the active ingredient are dissolved in the mouth and the active ingredient is swallowed in the form of a solution and, in the stomach, arrives in the form of a solution up to the ingested food and can be easily distributed therein.

The preparation of tablets that disintegrate orally from the active ingredient acarbose is problematic, since the active ingredient gives rise to slow and very hard solution tablets due to its physicochemical properties. A fast-disintegrating orally disintegrating tablet can be obtained when a large portion (< 50%) of water insoluble carriers is introduced into the tablet. However, the mouthfeel of these tablets is not satisfactory, since the large proportion of Insoluble excipients on the tongue is perceived as a strange rough substance.

Therefore, the development of the work for the present invention is concentrated in formulations having a reduced water-insoluble ratio.

Choosing excipients appropriately and the appropriate procedure (previous compaction of acarbose) formulations were found on the one hand with a pleasant sensation on the mouth and, on the other, very rapid release.

DESCRIPTION OF THE INVENTION The objective was achieved by means of the formulations presented below and the associated procedure: The formulation according to the invention is an orally disintegrating tablet containing 1 -30% acarbose and 40-90% water soluble carrier. It has a disintegration time of less than 60 s, preferably less than 45 s, more preferably less than 30 s, even more preferably less than 20 s. The water-soluble vehicle is the Ludiflash® product. Ludiflash® consists of: 90% mannitol, 5% crospovidone and 5% polyvinyl acetate. Similarly, it is possible to use as a water-soluble vehicle, optionally in a mixture with binders: mannitol, isomalt, sorbitol, lactose, starch, modified starch and maltodextrin. For the rapid solubility properties, it is important that the total moisture of the oral disintegration tablet is between 0-8%, preferably between 1-5%. The tablets have an abrasion below 1% and have a resistance to breaking that is between 20-50 N, preferably between 25-45 N. Before the formation of the tablets, the acarbose is processed to an average size of particle from 100 to 800 μ, preferably between 100-600 μ? t ?.

Examples Formulation 1 Formulation 2 Formulation 3 Formulation 4 Formulation 5 Formulation 6 In the first stage of the preparation, acarbose is subjected to granulation with a lubricant; subsequently the granulated substance is mixed with microcrystalline cellulose, such as Avicel for example. Preferably, the granulation is achieved by means of dry granulation. For this purpose, use is made, for example, of roller compactors, in which the powder is dosed through a narrow gap between two rotating rollers and compressed by means of pressure only to form flat and stretched strips, known as tapes At a later stage it is necessary to reduce the size of these strips so that they can be dosed directly into the interior of the tablet press. The average particle size of the compact material is between 100 and 800 μ? T ?, preferably between 100-600 μ? T ?. Most preferably, use is made of a compact material having a particle size of at least 15% >; 250 μ ?? After mixing other excipients, an orally disintegrating tablet containing 1-30% acarbose and 40-90% water-soluble carrier and 1-50% water-insoluble carrier is prepared subsequently from this compact material by means of tabletting. By means of prior compaction of the acarbose and subsequent mixing of the components, the area between the acarbose and the excipients necessary for disintegration is minimized. Therefore, tablets prepared in this way have a disintegration time of less than 60 s, preferably less than 45 s, more preferably less than 30 s, even more preferably less than 20 s. The total humidity of the orally disintegrating tablets is between 0 and 8%, preferably between 1 and 5%. The invention also relates to a method for preparing orally disintegrating tablets containing acarbose and other excipients, comprising the steps of 1. ) previously compact acarbose 2. ) mix with water insoluble vehicles, such as microcrystalline cellulose for example 3. ) mix with a water soluble vehicle and subsequent 4. ) tablet formation.

Optionally, point 2 and 3 can be combined.

Acarbose having a moisture content of between 0 and 5%, preferably between 1 and 4% is used. The preferred average particle size of the acarbose compact is between 1 and 200 μ? T ?. The tablets have an abrasion below 1% and have a resistance to breaking that is between 10-50 N, preferably between 15-45 N. Most preferably, use is made of a compact material of acarbose having a particle size of 15% > 250 μ? T ?.

It is common for all formulations that acarbose is not processed in pure form with the water soluble filler. The use of a pure form leads to hard tablets. By wrapping with Avicel in an intermediate stage, a rapid disintegration of the tablet can also be achieved with the addition of a water-soluble filler. An advantage of the water-soluble filler is that the formulation has a better mouthfeel and, also, greater stability against the disintegration time of the tablet. The tablets are characterized by a stability of at least 2 years, preferably 3 years.

Example: Determination of the disintegration time of the tablets comprising pure acarbose and pre-compacted acarbose.

Claims

1. An oral disintegration tablet, characterized in that it comprises: 1-30% acarbose, 40-90% water soluble vehicle and 1-50% water insoluble vehicle.

2. The tablet according to claim 1, characterized in that it has a disintegration time of less than 60 s.

3. The tablet according to claim 1, characterized in that it has a moisture content of between 0 and 8%.

4. The tablet according to claim 1, characterized in that it has a resistance to rupture of 10-50 N.

5. A method for preparing orally disintegrating tablets containing acarbose, characterized in that it comprises the steps of: a) p re-compact acarbose b) mix with water insoluble vehicles c) mix with a water soluble vehicle d) forming tablets, characterized in that acarbose having a moisture content of between 0 and 5% is used.

6. The method according to claim 5, characterized in that acarbose having an average particle size of 100 to 600 μ ?? is used.

7. The oral disintegration tablet according to claims 1 to 4, for the treatment of diabetes mellitus.